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Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL\u20106 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL\u20106 on ovarian cancer cell lines (SKOV3 and PA\u20101) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin\u2010related protein 1 (Drp1), a regulator of mitochondrial fission, and IL\u20106R in metastatic ovarian cancer tissues. Additionally, IL\u20106 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p\u2010Drp1(S637) to the active form p\u2010Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL\u20106 treatment triggered the activation of ERK1\/2, and inhibiting ERK1\/2 mitigated IL\u20106\u2010induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL\u20106\u2010induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient\u2010derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL\u20106. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer.<\/jats:p>","DOI":"10.1111\/cas.16064","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T04:39:57Z","timestamp":1709527197000},"page":"1536-1550","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mitochondrial fission enhances <scp>IL<\/scp>\u20106\u2010induced metastatic potential in ovarian cancer via <scp>ERK1<\/scp>\/2 activation"],"prefix":"10.1111","volume":"115","author":[{"given":"Juwon","family":"Lee","sequence":"first","affiliation":[{"name":"WCU Biomodulation, Department of Agricultural Biotechnology Seoul National University  Seoul Korea"},{"name":"Cancer Research Institute, College of Medicine Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngjin","family":"Han","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, College of Medicine Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soochi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"},{"name":"Paul F. 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